Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: One-year results of a 2-center prospective randomized trial

Abstract

This 2-center, prospective randomized study showed high immunosuppressive potency of both cyclosporine A and tacrolimus in combination with mycophenolate mofetil. No significant difference in incidence of acute rejection was observed between the 2 groups. Moreover, survival and incidence of infection were similar. Incidence of drug-related adverse events were similar, yet their spectrum was different.

Liposome-Mediated Combinatorial Cytokine Gene Therapy Induces Localized Synergistic Immunosuppression and Promotes Long-Term Survival of Cardiac Allografts

“…This finding is consistent with previous observations that, in the delayed-type hypersensitivity reactions, both cytokines are needed to induce optimal tolerance (18,29,41). A significant increase in CD4 ϩ to CD8 ϩ ratio that was only seen in combinatorial gene therapy group, not in single gene therapy groups, suggests that the preferential inhibition of CD8 ϩ cell may be beneficial and contributes to the prolonged allograft survival (2). IL-4 and IL-10 acts at different stages of the alloimmune-responsive process.…”

“…However, there are major obstacles about acute and chronic rejection. Systemically administering pharmacological agents can easily induce immunosuppression; however, it usually results in multiple, deleterious side effects requiring major dosage adjustments, and true tolerance is rarely achieved (1,2). Recently, the evolution of localized gene therapy for preventing cardiac allograft rejection has attracted attention.…”

Immunosuppression for lung transplantation

“…Currently, TAC accounts for 70% of all CNI-based maintenance immunosuppression, both at discharge and at 3 years post-transplant (28). This preference for TAC is supported by the extrapolation of data from other solid-organ transplants, and is at least not refuted by interim results from a prospective two-center European trial comparing the efficacy of CsA and TAC, when used in conjunction with mycophenolate mofetil (MMF) (29).…”

Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival

“…While the mean drug level required to prevent rejection has been well studied, little attention has been paid to the effect of erratic tacrolimus exposure, but with a satisfactory mean, in lung transplantation (15,(17)(18)(19)(20)(21)(22). There are good reasons to believe that erratic exposure may be just as deleterious as sub-therapeutic tacrolimus exposure, but this possibility has been little explored.…”